The glutathione S-transferases are a group of enzymes that have been shown to be active in the detoxification of certain drugs, carcinogens and metabolites. Increased expression of the placental form of the enzyme has been found in association with carcinogenesis and drug resistance. Some investigators have found increased expression of the placental form of the enzyme, measured by RNA slot blot and protein assays, to be inversely related to estrogen receptor positivity in malignant breast tumors. A study is currently underway to further evaluate this relationship using immunohistochemistry to determine GST-pi expression and estrogen receptor positivity in formalin-fixed paraffin embedded breast tumors. Preliminary studies utilizing immunohistochemistry have also demonstrated increased GST-pi expression in preneoplastic and neoplastic lesions of the uterine cervix. we are further evaluating this relationship using immunocytochemistry in cervical/vaginal biopsies, as well as cervical/vaginal smears. In addition, in situ hybridization for HPV DNA performed on the same specimens will enable us to explore possible relationships between GST-pi overexpression and various HPV types.